The mechanisms controlling the activity of T4 prehead proteinase in maturing the head of Bacteriophage T4 are being studied. This system is taken as a model for the regulation of intracellular proteolysis during virus infection of animal cells and the control of intracellular proteinases in uninfected cells. The specificity of the phage enzyme is studied by sequencing the genes of the known protein substrates for comparison with the peptides produced by cleavage in vitro. The activation of the proteinase zymogen is also to be studied in vitro using material purified from bacteria carrying a hybrid plasmid which expresses the phage gene. The physiological role of a protein inhibitor of the phage enzyme is to be determined from the characteristics of cleavage in vivo in a phage mutant which does not produce the inhibitor.